1. Field
Provided herein are CD47 fusion polypeptides and related compositions that may be useful for treating immunological diseases and disorders, including autoimmune diseases and disorders. The fusion polypeptides described herein alter immunoresponsiveness of the immune cell, such as by inhibiting production of cytokines by the immune cell.
2. Description of the Related Art
Viruses, such as members of poxvirus families, have the capability to evolve and/or the capability to acquire genes from the host that modulate an immune response of the host to the virus and/or that facilitate viral replication (Bugert and Darai, Virus Genes 21:111 (2000); Alcami et al., Semin. Virol. 8:419 (1998); McFadden and Barry, Semin. Virol. 8:429 (1998)). A cellular component in the host that is a ligand for a viral virulence factor may, therefore, be an important immunomodulatory target. Poxviruses form a group of double-stranded DNA viruses that replicate in the cytoplasm of a cell and that have adapted to replicate in numerous different hosts. Poxviruses, including variola virus, the causative agent of smallpox, and vaccinia virus, a prototype poxvirus widely used as a smallpox vaccine, have large genomes of nearly 190 kilobases, which could potentially encode more than 200 proteins (see, e.g., Goebel et al., Virology 179:247 (1990)).
Identification of poxvirus virulence factors that are capable of suppressing the host's immune system is useful for identifying cellular polypeptides that are effectors or modulators of an immune response and that can be modulated in a manner that is beneficial for treating immunological disorders, such as, for example, inflammatory diseases and autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus (SLE).
Immunological diseases and disorders afflict more than twenty million people in the United States. Many immunological diseases are debilitating and chronic and thus affect a patient's productivity, well-being, as well as general health. A need exists to identify and develop compositions that can be used for treatment and prophylaxis of such immunological diseases and disorders.